It is well known that people who snore are a source of disturbance and annoyance to those around them. In fact, snoring is a sound which comes from abnormal vibrations of the soft palate. Moreover, very often the snorer suffers from a blockage of the nasal fossae, which worsens the ailment.
It will be noted that a difference must be made between ordinary snorers and chronic snorers, who may be suffering from a serious ailment, namely, sleep apnoea syndrome (SAS).
The treatments which are currently in use consist of surgery (uvula-palatal-pharynogoplastic surgery), or of electronic signals which are applied to the brain and send out messages to the snorer which wake him and force him to change position. Other treatments such as acupuncture or medicinal treatments which consist in instilling nasal drops have also been used. Vasoconstrictors, which decongest the nasal mucus (U.S. Pat. No. 2,989,437) or surface-active agents which sometimes contain glycerine, such as those disclosed in U.S. Pat. No. 4,556,557, are also known. The surface-active agents may take the form of cationic, anionic or non-toxic surfactants, such as those used in commercialized products such as Phonarex.RTM. or Ronfulux.RTM., which are available in some European countries.
The above mentioned products attempt to hydrate the nasal mucus, but due to the short period of contact of these compounds with the mucus, it results in products that are not very efficient, except in the cases whereby they are applied repeatedly throughout the night. Moreover, some of these products are likely to cause nasal hemorrhages which may in certain cases be serious if these products are misused. The vasoconstrictors of the naphazoline, tetryzoline or xylometzaline types, or all those derived from phenylpropanolamine create a certain dependency and secondary effects whose symptoms take the form of a type of drug addiction.
These surface-active products have largely been abandoned as they do not have the characteristics required to remain in contact with the tissues of the nasal mucus for a sufficiently long period.
In view of the foregoing, it would be of great commercial value to produce a treatment for snoring that overcomes the disadvantages described above, and to offer snorers a new, highly effective composition, tolerated by the body and specifically, the nasal mucus, which is capable of treating or preventing snoring.
In accordance with the present invention, the new nasal solution comprises natural or semi-synthetic polymers of a high molecular weight such as mucopolyssacharides of the glycosaminoglycane type, which can be found either in their natural form, or which are synthesized xylanes that are extracted from certain types of wood, for example beech, and are then transformed by synthesis into sulfuric polyester sodium salt.
Thus, we can obtain pentosane polysulphate which is described in the French patent no. 1,050,576 dated Jun. 2, 1952 or the BS no. 2,227 dated Jul. 12, 1962.
Basically, these are analogous structures of natural sulphated mucopolysaccharide acids, such as sulfuric chondroitin acids, keratosulphates, dermatane sulphates, heparin, or other mucopolysaccharides such as hyaluronic acid. In each case, these are polyanions of a general type of structure: ##STR1##
These substances have properties which are sometimes comparable, but often vary one from the other. They are known under the class name of heparinoids, in spite of the fact that most of them, as is the case for chondroitin sulphate, or for pentosane polysulphate, no longer have an anti-clotting action which is characteristic of true heparin type substances as previously described. Thus, certain derivatives are used as anti-vital agents (Zbl. Bakt. Hyg. I Abt. Orig. 1977, A 237, pages 1-34), and others are used as fibrinolytic hypolipemiants as is the case for pentosane polysulphate (Arzneim. Forsch. 1972, 22, pages 759-763).
Others, such as chondroitin sulphate, have been described either as having properties which preserve the ocular tissues, or are able to play the role of a tear substituent (European patent no. 0063973). In the last case mentioned, certain fractions of chondroitin sulphate (type A) are used in preference to other fractions (B or C or mixtures of A+C).
These are always highly absorbent, high viscosity substances whose structure is often very similar to that of natural tissues such as cartilage, conjunctiva tissue, etc. For example, chondroitin sulphate A, instilled in the form of eye lotion at 3%, has revealed a major mucometic activity when applied to the rabbit eye, owing to its capacity of preserving the epithelial surface at the level of the microstructures (J. Fr. Ophtalmol. 1984, 1, pages 41-50).
The applicant has discovered that some polysacharides, whose molecular weight ranges between 1,000 and 1,000,000, are remarkably effective in their activity as far as the nose is concerned, and more especially in preventing snoring for a prolonged period of time. Most of these polyanionic substances described above have proved this. Polyanionic substances, such as heparin itself or heparinoids, may not be used to this end owing to the troublesome effects they have on the system itself. Thus, heparin has a major anti-clotting activity at the level of the nasal mucus or on the system, meaning that this substance can never be used in the new anti-snoring treatment.
On the other hand, applicant has learned that polysulphated derivatives of xylene, dextran, polyuronids or mucopolysaccharides, are well suited to treatment or prevention of snoring, given that they have no anti-clotting properties of their own. Moreover, they may also be applied in large doses without altering the nasal mucus and without causing systemic toxicity. In addition, it was discovered by accident that for some of the foregoing compounds, the nasal passages proved to be an excellent way in which to apply them; moreover, some of them even presented hypolipemiant properties.
Therefore, the applicant may well claim the discovery of new therapeutic indications, as well as a totally different method of presenting and applying the substances (nasal application) to those which have been previously advocated (i.e., capsules, injections, eye lotion).
In accordance with this invention, the new composition to prevent or treat snoring by means of nose drops applied in the form of solution, has as its main active constituent one of the mucopolysaccharides mentioned above, and more particularly, chondro it in sulphate sodium salt, whose molecular weight lies between 1,000 and 1,000,000.
The composition takes the form of a white powder obtained from fish or mammal cartilage. It has neither a smell nor a taste, and it does not decompose in water whose pH lies between 5 and 8 and in concentrations having a density is between 1 and 10%.
Apart from its above mentioned active constituents, and more precisely sodic chondroitin sulphate, the compositions for this nasal solution, must contain various formulating agents to enable them to be applied comfortably and easily to humans.
These constituents are essentially buffers, substances with isotonic properties and perfumes whose roles are well known. The choice of a preservative to be incorporated into the composition is a delicate one, given that the glycosaminoglycanes used in this invention are mainly polyanions which are negatively loaded, as previously indicated. Given that most of the antiseptics which can be used as preservatives are part of the chemical families which are positively loaded (as for example is the case of benzalkonium chloride, quaternary ammoniums in general, chlorohexidine salts, etc.), the choice of a nontoxic preservative which is well tolerated by the nasal mucus was in fact a delicate one. Thus, derivatives such as Imiduree and DMDM hydantoin might have been used in the final composition had their poor local tolerance not eliminated them from the list of available choices. The derivatives of p-hydroxybenzoic acid were not chosen either due to their allergising powers. The mercury derivatives, such as phenylmercury salts (nitrate, borate, acetate) were the only ones which presented the best safety/effectiveness ratio when they were used in very low concentrations (mg%).
Furthermore, when these water soluble mucopolysaccharide derivatives described above were combined with various substances of plant origin, we noticed that the clinical effectiveness of the final composition could be greatly increased. This is a particularly interesting case of a synergistic effect in the field of pharmaco-therapy.
These plant substances, among which we can list Belladonna, Sambucus and Bryonia, are they themselves synergised by various mineral constituents which are used in homeopathic concentrations. Preferably, the plant substances themselves may be diluted in to low concentrated forms, like those used in homeopathy "(CH, the preferred designation for Hahnemann centesimal [1/100] attenuations, which clearly indicates both the scale used and the method of attentuation [The Homeopathic Pharmocopela of the United States])".
The aqueous solutions well suited to nasal applications, may contain around 0.1% to 10% of their weight in soluble polysaccharide sodium salt, for example, pentosane sulphate, chondroitin sulphate and hyaluronic acid. It is recommended that these solutions be applied once before going to bed but they may be applied several times if required during the night.
The invention will no doubt be more easily understood from the description which follows, of which a part relates to a series of examples of nasal solutions, and another part concerns the clinical tests conducted using these compositions, or at least using one type of composition based on mucopolysaccharides chosen from the list which has been described above.